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Review
. 2019 Sep;67(9):701-715.
doi: 10.1369/0022155419849386. Epub 2019 May 22.

Novel _targets for Therapy of Renal Fibrosis

Niki Prakoura  1 , Juliette Hadchouel  1   2 , Christos Chatziantoniou  1   2
Affiliations
Review

Novel _targets for Therapy of Renal Fibrosis

Niki Prakoura et al. J Histochem Cytochem. 2019 Sep.

Abstract

Renal fibrosis is an important component of chronic kidney disease, an incurable pathology with increasing prevalence worldwide. With a lack of available therapeutic options, end-stage renal disease is currently treated with renal replacement therapy through dialysis or transplantation. In recent years, many efforts have been made to identify novel _targets for therapy of renal diseases, with special focus on the characterization of unknown mediators and pathways participating in renal fibrosis development. Using experimental models of renal disease and patient biopsies, we identified four novel mediators of renal fibrosis with potential to constitute future therapeutic _targets against kidney disease: discoidin domain receptor 1, periostin, connexin 43, and cannabinoid receptor 1. The four candidates were highly upregulated in different models of renal disease and were localized at the sites of injury. Subsequent studies showed that they are centrally involved in the underlying mechanisms of renal fibrosis progression. Interestingly, inhibition of either of these proteins by different strategies, including gene deletion, antisense administration, or specific blockers, delayed the progression of renal disease and preserved renal structure and function, even when the inhibition started after initiation of the disease. This review will summarize the current findings on these candidates emphasizing on their potential to constitute future _targets of therapy.

Keywords: CB1; Cx43; DDR1; chronic kidney disease; extracellular matrix; fibrosis; inflammation; periostin; therapeutic _target; transforming growth factor beta.

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Conflict of interest statement

Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Figures

Figure 1.
Figure 1.
Schematic illustration of the role of DDR1, periostin, Cx43, and CB1 during progression of renal disease. After an initial aggression of the kidney, different factors, cytokines, or signaling pathways upregulate the expression of DDR1, periostin, Cx43, and CB1. Each protein activates downstream receptors and pathways that lead to production of proinflammatory and profibrotic cytokines, inflammation, macrophage activation, energy depletion, apoptosis, and excess matrix production, which cumulatively contribute to renal fibrosis and CKD development. Abbreviations: DDR1, discoidin domain receptor 1; Cx43, connexin 43; CB1, cannabinoid receptor 1; CKD, chronic kidney diseases.
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